Polymorphisms in oxidative drug metabolism: relationship to food preference.

To determine whether a correlation exists between polymorphisms of oxidative drug metabolism and dietary preference, 29 poor metabolizers of dextromethorphan, 18 poor metabolizers of mephenytoin and 134 extensive metabolizers of both drugs were screened for their preferences for various food items. Poor metabolizers of dextromethorphan showed a diminished stated preference for cauliflower and coconut, and poor metabolizers of mephenytoin showed a diminished stated preference for spinach and cabbage.

The association between Type A behavior and change in coronary risk factors among young adults.

The association of Type A/B behavior pattern and changes in blood pressure, total serum cholesterol, serum triglyceride, body mass, and smoking was estimated in a cohort of 375 young Black and White men and women from a rural county in Central Kentucky between 1978-79 and 1985-88. Type A participants experienced significant increases in systolic (2.90 +/- 1.29 mmHg) and diastolic (3.80 +/- 1.17 mmHg) blood pressure and in cigarette smoking (3.26 +/- 0.89 cigarettes per day) over the eight-year follow-up period, but Type B participants experienced no change. Type A and B individuals showed similar changes in total serum cholesterol, serum triglyceride, or body mass. Differences between behavioral types in blood pressure were present for women but not men, and for Blacks but not for Whites. These findings suggest a possible significance of the Type A pattern for the development of cardiovascular risk of young adults.

The role of atmospheric pressure variation in the development of spontaneous pneumothoraces.

It has been postulated that spontaneous pneumothoraces (SP) develop because of rupture of subpleural blebs, and that atmospheric pressure changes (delta AP) may be contributory. A 5-year retrospective analysis of SP admissions was carried out to determine if delta AP do play a role in SP development. Using a 36-yr record of hourly delta AP, a normative background for delta AP was constructed. A fall in AP below the fifth, or a rise above the ninety-fifth percentile during these time periods, was classed as "unusual." Atmospheric pressure changes in the 4 days prior to SP were analyzed. The expected frequency of SP occurring by chance, if no relationship to delta AP existed, was also calculated. A total of 192 cases of SP was analyzed. Traumatic pneumothoraces were excluded. The majority of cases (72%) had been exposed to at least one "unusual" delta AP in the 4 days prior to onset of symptoms. Among those with four or more "unusual" exposures, SP occurrence was significantly more frequent than expected by chance alone (p less than 10(-10]. A strong positive association between delta AP and SP was not found in all cases, as delta AP are unlikely to be the only causative factor for SP. This finding of a relationship with ambient pressure changes lends support to the theory that SP develop as a result of rupture of subpleural blebs.

Blood pressure trends associated with changes in height and weight from early adolescence to young adulthood.

In children, blood pressure is more closely related to height and indices of maturation than to age. This study extends observations on the relationship between height, weight, maturation and blood pressure during early adolescence into young adulthood. Standardized measurements of blood pressure, height, and weight were initially obtained in all 14-15 year old adolescents (N = 304) in a rural Kentucky school system. Measurements were repeated 5 and 8 years later. Adolescents with relatively high blood pressures continued to have higher blood pressures as young adults. Increases in systolic and diastolic blood pressure over time were related to increases of relative weight in both sexes (p less than 0.0001 and p less than 0.005, respectively), and in males increases of systolic blood pressure were related to increases of height (p less than 0.005). However, males who attained their full height at younger ages had higher blood pressures both during adolescence and subsequently, as young adults. Thus blood pressure of young adults is related to blood pressure in adolescence, relative weight and change in relative weight since adolescence, and in males to age of maturation as determined by the age at which adult height is attained.

Impact of a rural high blood pressure control program on hypertension control and cardiovascular disease mortality.

Kentucky is a predominantly rural state with relatively high death rates from hypertension and cardiovascular disease. We report the results of a community-based high blood pressure control educational program undertaken in two rural counties of southeastern Kentucky. In the intervention counties, systolic and diastolic blood pressures of both men and women decreased despite the five-year increase in age; moreover, hypertension was better controlled after the program, and substantial decreases in deaths due to cardiovascular disease were seen. These differences were greater among men in the two regions than among women. The results of this program suggest that, in sparsely populated rural areas, existing resources and programs can be successfully utilized in a communitywide cardiovascular disease risk reduction educational program.

Blood pressure related echocardiographic changes in adolescents and young adults.

In 1973, standardized blood pressure measurements were obtained in 837 high school students in Bourbon County, Kentucky, a rural county with a high prevalence of individuals with systemic hypertension. In 1978, follow-up measurements of blood pressure were performed in selected individuals who were in the high, intermediate, and low ranges of the initial sex-specific blood pressure distributions. Relative rank order of initial blood pressure measurements over the five-year period was maintained. The results of this population-based study provided an opportunity to evaluate the cardiac status in young adults with relatively high blood pressures maintained over five years. Standard m-mode echocardiographic examinations were, therefore, performed over five years. Standard m-mode echocardiographic examinations were, therefore, performed at the time of follow-up. In individuals in the low and intermediate ranges for systolic blood pressure, indices of ventricular hypertrophy were directly correlated with blood pressure level. Among individuals with higher values for systolic blood pressure, after adjusting for the effects of relative body size, indices of ventricular hypertrophy were not significantly different from those noted in the intermediate group. Indices of cardiac performance and estimated left ventricular systolic wall stress were, however, significantly elevated in this "high" blood pressure group. Early in the course of systemic hypertension increased wall stress, rather than hypertrophy, appears to be the primary cardiac manifestation of elevated systolic blood pressure.

Blood pressure trends with aging.

In industrialized societies, blood pressure increases with age, and blood pressure at one age is related to blood pressure at an earlier age. Blood pressure is also related to weight, weight change, and maturation. This paper reviews the association of growth and maturation with blood pressure and the evidence for blood pressure "tracking" with age. Additional longitudinal studies are required to determine if blood pressures before puberty are related to blood pressures of sexually mature young adults. Adolescents with "gestational" hypertension also have relatively high blood pressures at long-term follow-up. Thus, it may by possible to identify young individuals who are at increased risk for cardiovascular disease.

Blood pressure of young mothers and their children after hypertension in adolescent pregnancy: six- to nine-year follow-up.

To determine if gestational hypertension during adolescent pregnancy is associated with subsequently elevated blood pressure, blood pressures were measured in young mothers 3-6 years and again at 6-9 years after their first pregnancy. Follow-up study groups were selected from an original study population of 409 pregnant adolescent women followed at the university of Kentucky Medical Center between 1971 and 1974 in a specially designated Young Mothers' Program. Blood pressures measured during the first and second follow-up surveys were highly correlated. Compared to matched control subjects who remained normotensive throughout pregnancy (n = 54), women with a history of hypertension during pregnancy (n = 70) were heavier, maintained higher blood pressure, and had a greater incidence of hypertension in subsequent pregnancies. At the second follow-up survey, systolic blood pressure and body weight of male children born to women who experienced gestational hypertension were greater than respective values in males born to women with normotensive pregnancies. Blood pressures of female children of the two groups of young mothers did not differ. Overall, blood pressures and body weights of young mothers correlated with blood pressures and body weights of both their children and their own mothers. The results suggest that gestational hypertension may unmask a tendency for hypertension.

Low renin-aldosterone in "prehypertensive" young adults.

PRA is suppressed in approximately 25% of patients with essential hypertension. To determine if renin suppression precedes the onset of hypertension, PRA and plasma aldosterone were measured before and after treadmill exercise in 129 young adults with relatively high, intermediate, or relatively low blood pressures sustained over 5 yr. PRA and aldosterone responses to exercise were lower (P less than 0.01) in the high blood pressure group. In contrast, plasma renin substrate was lower (P less than 0.01) in the low blood pressure group. Unrelated to blood pressure, PRA, but not aldosterone, was lower in black than in white subjects both before and after exercise. In conclusion, renin suppression precedes the onset of hypertension and may be an appropriate response to higher levels of arterial pressure.

Improved prediction of fetal lung maturity in diabetic pregnancies: a comparison of chromatographic methods.

Following planned termination of pregnancy, infants of diabetic mothers have shown a continued vulnerability to the respiratory distress syndrome (RDS), suggesting false positive results on fetal lung maturity testing. We studied the adequacy of the standard one-dimensional chromatographic lecithin/sphingomyelin (L/S) ratio for predicting RDS in 56 diabetic and 50 nondiabetic pregnancies. An exceptionally low incidence of RDS was noted for the study (0.95%) as well as for diabetic pregnancies alone (1.85%). The clinical results were further compared to a new method for determining L/S ratios and identifying other pulmonary phospholipids by two-dimensional chromatography. Values for two-dimensional L/S ratios were significantly lower from 36 through 38 weeks' gestation (P less than 0.01), suggesting improved accuracy and a lessened risk for false positive results in preterm deliveries. Positive identification of amniotic fluid phosphatidylglycerol (PG) was related to increasing L/S ratios (P = 0.001), but only 50% of nondiabetic and 16.7% of diabetic amniotic fluid samples contained PG when the L/S was 2:1 or greater (P = 0.02). The identification of PG serves to confirm fetal lung maturity, but the L/S ratio remains the best available indicator of fetal lung maturity for all high-risk pregnancies.

Nicotine exposure and Parkinson disease.

The observed inverse relationship between smoking and Parkinson disease has prompted suggestions that nicotine, a centrally active agent, might protect against the disease. In this case-control study, cases were found to have ever regularly smoked cigarettes significantly less frequently than sex-, race-, and age-matched neighbors. This report analyzes the detailed smoking histories of cases and neighbors to see if these histories support the nicotine protection hypothesis. Estimated nicotine exposure before age at onset of symptoms for smoking cases was 186.1 g; for smoking controls it was 208.3 g (p = 0.34). Among the cases, severity of disease was not related to the extent of nicotine exposure before disease onset. Age at onset of symptoms for smoking cases (52.7 years) was not delayed (57.8 years for nonsmoking cases). Since the study was unable th find further support for the nicotine protection hypothesis, it is concluded that the observed inverse relationship between smoking and Parkinson disease is likely explainable by other factors, such as selective mortality or pre-morbid behavioral and/or constitutional changes.

Bioassay of a cigarette smoke fraction. I. Examination of dose-response relations and dilution bioassay assumptions in a ciliostasis system.

Ciliostasis times of the water-soluble smoke fraction of the University of Kentucky 1R1 Reference Cigarette and experimental cigarettes were compared in the hamster tracheal ring system. Dose-response relations were critically examined, and the assumptions of a dilution bioassay were tested. The model in which a logarithmic transformation was used for both mean time to ciliostasis and smoke sample concentration gave the most satisfactory linear fit. At appropriate concentrations, the ciliostatic responses of the test tobacco smokes were found to be parallel to those of the 1R1, supporting the validity of the dilution bioassay assumptions. Details of experiments and analyses are presented as examples of some of the steps required to establish valid bioassay systems.

Bioassay of a cigarette smoke fraction, II. Experimental design and potency estimations.

A series of experimental designs aimed at collecting and analyzing ciliostasis data in the most efficient and statistically valid manner was examined. The design that proved best for assessing water-soluble tobacco smoke samples in the hamster tracheal ring system utilized two dose levels of the University of Kentucky 1R1 reference cigarette (which functions as a reference as well as a continuing check on the dose-response relation in each experiment) plus several test tobacco smoke samples, each at a single dose level. A pair of animals formed the basis of a randomized block design, with one of the technician X sample preparation degrees of freedom confounded with animal differences within a pair. Assessment of the test samples can thus be expressed in terms of potency relative to the 1R1 reference. Control chart procedures were an essential facet of the system. Details of experiments and methods of data analysis are presented as examples of some of the steps required ot establish valid bioassay systems.

Influence of potassium cardioplegia versus ischemic arrest on regional left ventricular diastolic compliance in humans.

To compare the effects of hypothermic ischemic arrest versus hypothermic potassium cardioplegia, regional left ventricular performance was monitored in 20 adult male patients undergoing saphenous vein bypass operation. Twelve patients received ischemic arrest (Group 1), and 8 received potassium cardioplegia (Group 2). Groups 1 and 2 did not differ in left ventricular ejection fraction (0.62 versus 0.60), number of bypassed vessels (3.7 versus 3.4), mean cross-clamp time (75 versus 63 minutes), or mean cardiopulmonary bypass time (182 versus 170 minutes). Before cardiopulmonary bypass was begun, a pair of ultrasonic crystals was secured in the left ventricular anterior myocardium to measure segment motion and a micromanometer-tipped catheter was placed in the left ventricular chamber. All patients received a saphenous vein bypass graft to a vessel supplying the anterior left ventricular wall in the region of the ultrasonic crystals. Comparison of changes in systolic measurements revealed no significant differences between Groups 1 and 2. After saphenous vein bypass grafting, the left ventricular end-diastolic pressure (11.4 to 17.0 mm HG) and modulus of left ventricular segment stiffness (0.37 to 0.67, p less than 0.02) were elevated in Group 1 but no changes were observed in Group 2 (14.0 to 15.6 mm Hg, and 0.16 to 0.24, respectively). Compared with hypothermic ischemic arrest, hypothermic potassium cardioplegia is not associated with an increased left ventricular diastolic stiffness shortly after saphenous vein bypass grafting in humans.

Cigarette smoking and Parkinson disease: 1. Comparison of cases with matched neighbors.

In previous studies, there were fewer cigarette smokers among persons with Parkinson disease than among other patients. We reinvestigated this phenomenon, using nonpatient controls. In home interviews with 237 Parkinson patients and 474 age-, sex-, and race-matched neighbors, we inquired about consumption of tobacco, coffee, tea, and alcohol. All Parkinson patients were diagnosed by a neurologist, had two or more cardinal features of parkinsonism, and had not received chronic phenothiazine therapy. One hundred fifty (63%) of 237 cases and 224 (47%) of 474 controls never smoked cigarettes (p < 0.0001). Significantly different smoking rates were also preset at 10 and 20 years before the onset of parkinsonism.

Maternal perception of fetal movement and perinatal outcome.

The maternal perception of fetal activity was studied in 306 clinic patients who counted for 2 predetermined hours each day. "Alarming" and "reassuring" fetal movement patterns were defined from statistical analysis. All reassuring fetal movement patterns were followed by reactive nonstress tests (NSTs), and the 2 nonreactive NSTs were preceded by alarming fetal activity. No relationship between urinary estriol determinations and prior fetal activity was present. Excluding congenital anomalies, perinatal distress was infrequent with prior reassuring fetal activity and arose primarily from intrapartum factors. An alarming fetal movement pattern was twice as frequent in high-risk pregnancies and was associated with a significantly greater risk of subsequent perinatal distress (P less than .0001). Clinical applications of the proposed technique are discussed.

Correlates of adolescent blood pressure at five-year follow-up.

In 1973, standardized measurements of blood pressure (BP), height, and weight were obtained on all adolescents attending high school in a rural Kentucky county. In 1978, a 5-year follow-up BP study was undertaken of all adolescents who were 14-15 years old at the time of the initial survey (n = 310), and of selected 16-19 year olds who were in the high, intermediate, and low ranges of the initial sex-specific BP distributions (n = 198). Follow-up measurements included height, weight, and BP on all subjects and, in addition, overnight sodium (Na) excretion, serum cholesterol, glucose, triglyceride, and uric acid concentrations on the older group. Our findings indicate that BP in young adults is related to BP in adoleslcence, change in relative weight since adoleslcence, and current relative weight. Relative rank order of initial BP levels were maintained over the 5-year period in both the younger and older groups. Additional cardiovascular disease risk factors were found to cluster in young adults with high BP, and clustering of risk factors may, in part, be related to high relative weight.

Smoking and abortion.

PIP: This is a letter criticizing the conclusions of a previously published study regarding the association between maternal smoking and spontaneous abortion. The tabular presentation of the data are said to skew the results. It is pointed out that the data show the risk of spontaneous abortion to be significantly greater only for young smokers. Interpretation of any possible association between smoking and spontaneous abortion should consider the reason for the smoking, e.g., if the woman were smoking out of worry for a troubled pregnancy. The study by Kline et al. did not control for marihuana use or drinking, both of which behaviors might also have had a relationship to the spontaneous abortion. The trauma of abrupt withdrawal might be a greater risk for a smoking pregnant woman than gradual reduction to lower levels consistent with a trouble-free pregnancy.^ieng